Hexamerization of p97-VCP is promoted by ATP binding to the D1 domain and required for ATPase and biological activities.

The 97-kDa valosin-containing protein (p97-VCP or VCP), a hexameric AAA ATPase, plays an important role in diverse cell activities, including ubiquitin-proteasome mediated protein degradation. In this report, we studied dissociation-reassembly kinetics to analyze the structure-function relationship in VCP. Urea-dissociated VCP can reassemble by itself, but addition of ATP, ADP, or ...
ATP-gamma S accelerates the reassembly. Mutation in the ATP-binding site of D1, but not D2, domain abolishes the ATP acceleration effect and further delays the reassembly. Using hybrid hexamers of the wild type and ATP-binding site mutant, we show that hexameric structure and proper communication among the subunits are required for the ATPase activity and ubiquitin-proteasome mediated degradation. Thus, ATP-binding site in D1 plays a major role in VCP hexamerization, of which proper inter-subunit interaction is essential for the activities.
Mesh Terms:
Adenosine Triphosphatases, Adenosine Triphosphate, Animals, Binding Sites, Cell Cycle Proteins, Cysteine Endopeptidases, Kinetics, Multienzyme Complexes, Mutagenesis, Site-Directed, Proteasome Endopeptidase Complex, Protein Denaturation, Protein Structure, Tertiary, Protein Subunits, Structure-Activity Relationship, Ubiquitin, Urea
Biochem. Biophys. Res. Commun.
Date: Jan. 10, 2003
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